Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-gamma, Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A beta 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662. a PPAR-gamma antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-gamma agonistic effect, also inhibited A beta-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for A beta showed the reduced A beta deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings Suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-gamma activation, Could exert a stronger effect. (C) 2008 Elsevier Inc. All rights reserved.